This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks (NCT00462709), a na phase 3 study. The primary outcome is Frequency of All HAE Attacks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00462709 |
| Phase | Phase 3 |
| Condition | Hereditary Angioedema |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 146 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Shire |
| Results posted | Yes |
2. Clinical Question
Population
People with hereditary angioedema who received at least one prophylactic dose of C1INH-nf were included in the ITT-E population. The registry record gives this population as N=146. Screening attack-frequency data were reported by 137 subjects; data were missing for 9.
Intervention
The intervention was open-label C1 esterase inhibitor [human] (C1INH-nf), administered intravenously at 1,000 Units every 3 to 7 days. The stated objective was to evaluate its safety and efficacy when used prophylactically to prevent acute HAE attacks.
Comparator
There was no randomized comparator group. The registry lists allocation as NA and the study model as single group. Any comparison with screening or with an external group would therefore not be a randomized, like-for-like treatment comparison.
Primary question
The primary endpoint was the frequency of all HAE attacks, expressed as attacks per month, over the duration of the study. The registry defines an attack as a discrete episode in which a subject progressed from no angioedema to symptoms of angioedema. The result for this endpoint is not reported in the registry record, so the size and precision of the observed attack frequency cannot be assessed from the record.
3. Trial Design
This was a completed phase 3 study with an open-label, single-group design. The registry lists enrollment of 146, allocation as NA, and masking as none. It identifies Shire as the sponsor. The listed intervention was C1 esterase inhibitor [human] (C1INH-nf), a biological treatment.
The intervention description specifies intravenous administration of 1,000 Units every 3 to 7 days. The study objective was to evaluate prophylactic use of C1INH-nf for prevention of acute HAE attacks. The official title also refers to treatment in acute attacks, but the primary endpoint listed in the record concerns the frequency of all HAE attacks during the study. The endpoint result itself is not reported in the registry record.
The study began on 2006-06-27, reached primary completion on 2009-03-31, and is listed as completed. These dates describe the study record; they do not specify each participant’s time receiving treatment or the amount of follow-up available for each person. Individual treatment duration and participant-level follow-up details are not reported in the registry record.
Because there was no randomized comparator and no masking, the study can describe outcomes observed among participants receiving the intervention, but the design does not provide a randomized estimate of how those outcomes would differ under another treatment or no treatment. Open-label status also means that participants and investigators knew the treatment being given. The registry record does not report a protocol-level rationale for the design, a sample-size justification, or details of how potential sources of bias were addressed.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Open-label C1INH-nf |
|---|---|
| STARTED | 146 |
| COMPLETED | 79 |
| NOT COMPLETED | 67 |
Reasons for not completing this period:
| Reason | Open-label C1INH-nf |
|---|---|
| Transitioned to commercial C1INH-nf | 40 |
| Lost to Follow-up | 10 |
| Withdrawal by Subject | 8 |
| Transferred to LEVP2006-1 (NCT00438815) | 3 |
| Death | 2 |
| Logistical reasons | 2 |
| Physician Decision | 1 |
| Withdrew to start treatment with Cetor | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat Efficacy (ITT-E) Population (N=146; the number of subjects who received at least one prophylactic dose of C1INH-nf for the prevention of HAE attacks). HAE attack frequency was reported by 137 subjects at screening (i.e., data were missing for 9 subjects).
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Open-label C1INH-nf |
|---|---|---|
| Participants analysed | 146 | |
| Age, Continuous | years | 36.5 (SD 16.48) |
| Sex: Female, Male: Female | Participants | 112 |
| Sex: Female, Male: Male | Participants | 34 |
6. Primary Endpoint
The registry lists the primary outcome as Frequency of All HAE Attacks, measured over Duration of the study.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | attacks per month |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is titled “Frequency of All HAE Attacks” and is expressed in attacks per month. It covers the duration of the study. The registry defines an attack as a discrete episode in which a subject progressed from no angioedema to symptoms of angioedema. This definition sets the event boundary used to distinguish one attack from another.
The endpoint is a frequency measure: it describes how often attacks occurred, rather than the severity or duration of an individual attack. A monthly rate provides a common time scale for describing attack frequency, while the stated study timeframe indicates that the measure concerns the study period. The registry identifies the primary summary as a median with full range. In general, a median describes the middle of an ordered set of observations, and a full range describes its lowest and highest observed values. A range is not a confidence interval and does not, by itself, quantify uncertainty around the median.
The registry record gives the endpoint definition and identifies the ITT-E population, but it does not report the median or full range. It therefore does not provide the numerical primary result or enough information to assess its precision. The 137 subjects with reported screening attack frequency are described in the population note; those screening data should not be mistaken for the study’s primary endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the question the trial was designed to address: the frequency of all HAE attacks among participants receiving prophylactic C1INH-nf. It also specifies the attack definition, the attacks-per-month unit, the study-duration timeframe, and a median with full range as the intended summary. However, the numerical result for this endpoint is not reported in the registry record. There is consequently no posted median or range to interpret, and no basis in the record for describing the observed attack frequency as higher or lower than another value.
The record identifies an ITT-E population of N=146, defined as subjects who received at least one prophylactic dose. It says that screening attack-frequency data were reported by 137 subjects and missing for 9. These screening-data counts do not supply the missing primary endpoint result. Nor do they establish how many participants contributed to the endpoint analysis, because an endpoint analysis population or analysis count is not reported in the registry record.
The design also limits what can be inferred. A single-group, open-label study without randomized allocation can describe outcomes observed during treatment, but it cannot isolate a treatment effect from changes that might occur over time or from other influences. There is no concurrent randomized control group against which to estimate a treatment contrast. The registry record does not report an adjusted comparison, a sponsor-reported hazard ratio, or a statistical test for the primary endpoint.
Precision cannot be judged from the posted endpoint information. A median and full range, if reported, would describe the observed distribution, but would not by themselves establish the uncertainty around the median. The record does not report a confidence interval or other uncertainty measure for the primary result. With neither a numerical endpoint estimate nor an uncertainty measure, the magnitude and precision of the result cannot be evaluated from this registry record.
Any planning illustration based on a stated fraction of an observed effect is a hypothetical design calculation, not observed trial power. The record describes such illustrations as using equal allocation, despite this trial’s single-group design. Those assumptions do not turn the study into a randomized comparison or supply a missing endpoint estimate. No numerical planning result is reported in the registry record.
9. Statistical Methods Explained
What does a median summarize?
General statistical explanation: a median is the central value after observations are ordered. It is useful when a typical value is of interest and the distribution may not be well represented by an arithmetic average. The median does not describe all aspects of the distribution, so the registry’s pairing of the median with the full range would, if values were reported, give information about both the center and the observed extremes.
For this endpoint, each observation concerns attack frequency in attacks per month over the study duration. The record labels the summary as a median with full range, but gives neither the median nor the range. No numerical description of the observed distribution can therefore be drawn from the registry entry.
What does a full range tell the reader?
General statistical explanation: the full range extends from the smallest to the largest observed value. It shows how far apart the observed extremes are, but it is sensitive to those extremes and does not indicate how observations are distributed between them. It is also distinct from a confidence interval. A confidence interval is an uncertainty summary for an estimate; a range describes observed data values. The registry record does not list a confidence interval for the primary endpoint.
Why does the single-group design matter?
General statistical explanation: a treatment contrast requires a reference outcome under a comparator condition. Random allocation can help make treatment groups comparable, on average, with respect to factors that could affect outcomes. In a single-group study, the observed outcome has no concurrent randomized reference group. A change from screening, if reported, would be a within-group comparison and could reflect influences other than the intervention. The registry lists allocation as NA and the model as single group, so a randomized treatment contrast is not available from the design described.
The open-label designation means masking was absent. General statistical explanation: awareness of treatment can affect reporting, clinical decisions, and outcome assessment, depending on the endpoint and how it is collected. The registry defines an attack, but does not report details of endpoint adjudication or safeguards intended to limit assessment bias. Those details are not reported in the registry record.
How should uncertainty be read?
General statistical explanation: an estimate describes the result in the observed data, while an uncertainty measure describes how much imprecision is compatible with those data under the analysis assumptions. A confidence interval is one common way to express uncertainty around an estimate. It is not a guarantee that a particular value is true, and its interpretation depends on the design and analysis. Since the registry record does not report the endpoint estimate or a confidence interval, neither the observed magnitude nor its statistical precision can be evaluated.
The record lists zero analysis records. This means the registry entry does not include a posted analysis result to interpret; it does not establish what analyses may have been conducted outside the registry. No analysis method, model specification, or primary-endpoint test is reported in the registry record.
What are planning illustrations?
General statistical explanation: a sample-size calculation asks how much information a future study might need under chosen assumptions. It is not a measurement of how likely the completed trial was to detect an effect after the data have been observed. The registry’s description of planning illustrations specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. It distinguishes total events for time-to-event illustrations from participants per arm for other illustrations.
These are planning assumptions, not features of the trial design described in the registry. The study is listed as single group, not as an equal-allocation, two-arm randomized comparison. No numerical planning illustration is included in the registry record, and no observed endpoint effect is reported there to assess against such an illustration. Planning figures, where presented, should not be read as observed power or as evidence of a treatment effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures and identifies Frequency of All HAE Attacks as the primary endpoint. It lists no analysis records. A multiplicity adjustment plan, hierarchy for testing outcomes, or explanation of how multiple statistical tests were handled is not reported in the registry record. Without analysis results or a stated testing strategy, the chance of false-positive findings across multiple tests cannot be evaluated from this entry.
The population note says the ITT-E population included N=146 subjects who received at least one prophylactic dose. It separately states that screening attack-frequency data were reported by 137 subjects and were missing for 9. This is a specific report about screening data. The record does not say whether those missing screening values were imputed, excluded from a calculation, or handled in another way.
The screening-data note should not be treated as a complete account of missingness for the primary endpoint. The number contributing to the endpoint result, missing endpoint data, reasons for missing data, and any methods for handling them are not reported in the registry record. The ITT-E population definition indicates who was included in that population, but does not by itself establish how every outcome was analyzed.
Interim analyses, a statistical analysis plan, and a sample-size justification are not reported in the registry record. These omissions limit assessment of how outcomes were selected and analyzed, but do not establish that such plans or analyses did not exist outside the registry entry.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Open-label C1INH-nf | 0 | 146 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Open-label C1INH-nf | 9 of 146 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Open-label C1INH-nf |
|---|---|---|
| Headache | Nervous system disorders | 3 of 146 |
| Rash | Skin and subcutaneous tissue disorders | 3 of 146 |
| Nausea | Gastrointestinal disorders | 2 of 146 |
| Phlebitis | Vascular disorders | 2 of 146 |
For the Open-label C1INH-nf group, the registry lists 146 at risk for serious adverse events and 0 in the serious affected field. It lists 146 at risk for other adverse events and 9 in the other affected field. These are the counts recorded for the listed group; the registry entry does not provide event descriptions in the serious-terms list, which is empty.
The record’s death field is null. A null value does not provide a death count, so deaths are not reported in the registry record. The other-adverse-event count is not accompanied by event terms or further detail in the information, and should not be interpreted as a count of a particular type of event.
These safety counts are descriptive. With no comparator group, they do not establish whether the observed counts differ from what would have occurred under another treatment or without treatment. The record also does not provide details such as event timing, severity grading, or exposure-adjusted rates. The counts therefore offer only a limited view of the safety information recorded for this group.
12. What the Result Does, and Does Not, Mean
The record documents a completed, open-label, single-group phase 3 study of prophylactic C1INH-nf in hereditary angioedema. It specifies an intravenous regimen of 1,000 Units every 3 to 7 days, defines the primary endpoint as frequency of all HAE attacks, and identifies the ITT-E population. It also reports the number of subjects with screening attack-frequency data and the listed adverse-event counts.
Those details do not establish the result for the primary endpoint. Its median and full range are not reported in the registry record, nor is a confidence interval or statistical test. The posted entry therefore does not reveal the observed attack frequency during the study or how precisely it was estimated. The screening-frequency reporting note is not a substitute for those results.
The study design also does not support a randomized comparison. Since the record describes one open-label group with no randomized comparator, observed outcomes cannot be attributed to the intervention through a between-group treatment contrast. A before-and-after comparison, if one were available, would not by itself separate treatment effects from other changes over time; such a result is not reported in the registry record.
The safety fields describe counts for the listed group, but do not provide a comparative safety estimate or detailed event information. The death count is not reported in the registry record. Overall, the entry supplies useful information about the study question, design, endpoint definition, population, and selected safety counts, while leaving the principal efficacy result and its precision unavailable. These limits apply to what can be concluded from the registry record and do not determine what may be available in other sources.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design and result reporting must be considered together. A clearly named primary endpoint and a defined attack event identify what the investigators intended to measure. The attacks-per-month unit and median-with-full-range summary also indicate the intended form of the result. But an endpoint definition alone cannot show what was observed: the primary numerical result is not reported in the registry record.
The single-group, open-label structure is equally important. Such a design can document outcomes and safety observations among treated participants, but without randomized allocation and a concurrent comparator it cannot estimate a randomized treatment contrast. The registry’s listed group and population counts do not overcome that design limitation.
The entry also illustrates why missingness must be interpreted narrowly. It reports missing screening attack-frequency data for 9 subjects, but does not describe missingness in the primary endpoint analysis. Treating the screening note as evidence about all endpoint data would go beyond what the record states. Similarly, a null death field is not a reported zero count.
Finally, planning calculations and observed results answer different questions. Planning illustrations depend on assumptions and are not observed power. In this case, the stated equal-allocation assumption does not match the single-group design listed for the trial. Keeping that distinction clear prevents hypothetical design calculations from being mistaken for evidence about the trial’s outcome. The record’s chief statistical lesson is that study design, endpoint definition, analysis reporting, and uncertainty information each contribute different pieces of an interpretable result.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting efficacy is that the registry record does not report the primary endpoint value. Although it specifies a median and full range for attack frequency, neither is given. No uncertainty interval, test result, or analysis details for this endpoint are reported either. Consequently, the magnitude and precision of the primary outcome cannot be assessed.
The single-group, open-label design has no randomized comparator. Observed outcomes in the treatment group cannot, on their own, distinguish an intervention effect from other influences. Masking was absent, and details about outcome adjudication or procedures for reducing assessment bias are not reported in the registry record.
The record reports missing screening attack-frequency data for 9 subjects, but does not describe missing primary endpoint data or the method used to handle missing observations. It also does not report individual follow-up duration, endpoint analysis counts, or reasons for missing data. The population note identifies the ITT-E population, but does not resolve these analysis details.
The safety record is limited to the listed counts. Serious adverse-event terms are not listed, other adverse-event terms are not given, and the death field is null rather than a reported count. Event timing and other descriptive details are not reported in the registry record. Finally, a multiplicity strategy, interim analyses, sample-size justification, and statistical analysis plan are not reported. These gaps constrain interpretation of the registry entry; they do not establish that the information is unavailable elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks — NCT00462709.
- Registry record last updated 2021-06-08; status last verified 2021-05.
- Results first posted 2010-05-03.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes NCT00462709, a completed phase 3, open-label, single-group study sponsored by Shire. It evaluated C1INH-nf for prophylaxis against acute HAE attacks. The listed regimen was 1,000 Units intravenously every 3 to 7 days. The study began on 2006-06-27 and reached primary completion on 2009-03-31.
The primary endpoint was frequency of all HAE attacks, measured in attacks per month over the duration of the study and summarized as a median with full range. The ITT-E population was N=146; screening attack frequency was reported by 137 subjects and missing for 9. The primary endpoint result, its uncertainty, and a statistical analysis are not reported in the registry record. The safety fields list 0 serious affected and 9 other affected in the treatment group; the death count is not reported.